The goal is not extreme life span but something they call “health span.” Rather than getting heart disease or cancer in our fifties or sixties and needing expensive treatments and drugs to keep us alive (if they do) until we’re 75, we will age more slowly. We will still get these chronic diseases, but 10 or 20 years later, shortening considerably the time we spend in hospitals and nursing homes and the money we, and society as a whole, have to spend on health care. “What we would like to do,” Sharp says, “is prevent a lot of things that would put you into the hospital prematurely. The end is likely to be bad no matter what, but we’d like to compress the time that we have to do this intensive type of stuff.”
That both health span and life span are to a large extent determined by our genes is one of the more obvious and yet unexpected findings to come out of recent studies of centenarians, the oldest of the old. It is obvious because different species of animals age at different rates. Mice will last about three years, but after two they are likely to be getting frail or starting to succumb to cancer, organ failure, and diabetes. The same things happen in dogs at around 10 years and in horses at closer to 20. Chimpanzees take 30 years and humans typically 60 or more before the process of decrepitude begins. Rats and tree squirrels are virtually the same size and often live in the same environments, yet rats will live 3 or 4 years and squirrels as many as 20. Clearly some genetic mechanism must be determining how quickly each animal ages.
Still, when Barzilai and his colleagues questioned the near centenarians as part of their aging studies, the genetic determinant of longevity took the researchers by surprise. “When we started recruiting 100-year-olds,” Barzilai says, “we noticed something interesting. They have a family history of longevity. When we ask them, among other things, ‘Why do you think you lived to be so old?’ they usually say, ‘What do you mean? All my brothers and sisters are over 100.’ Or ‘My mother was 102; my grandfather was 108.’
“Then we say, ‘OK, tell us really the truth. You ate yogurt your whole life. You were a vegetarian.’ But the interesting thing is, we have only 2 percent vegetarians. We have none who exercised regularly, and 30 percent were overweight or obese back in the 1950s, when not that many people were overweight or obese. Almost 30 percent have smoked two packs of cigarettes for more than 40 years. We have one woman, alive now—she’s 107—who celebrated 95 years of two-pack-a-day cigarette smoking. She had four siblings in my study. All of them were over 100. One younger sister died at 102, the poor thing.”
This is not to say that smoking cigarettes won’t prematurely kill the rest of us, or that exercising regularly won’t make us live longer. “What I tell people,” says Steven Austad, an expert on the biology of aging at the University of Texas Health Science Center, “is that if you want to live to be a healthy 80-year-old, you have to eat right and exercise, et cetera. If you want to live to be a healthy 100-year-old, you have to have the right parents.” The ultimate aging clock moves by order of our genes. The genes can be influenced by the environment, lifestyle, and diet, but only finding the genes and deciphering their action will allow us to bottle and distribute the sauce.
Despite the recent explosion of life-extension research, the single most important observation in the field—the best clue about the nature of that special sauce—was first made three-quarters of a century ago. In 1935, the Cornell University nutritionist Clive McCay reported that feeding rats just barely enough to keep them alive extended their life span by as much as 50 percent. Several years later, a Chicago pathologist named Albert Tannenbaum found the same thing in mice. Feed these animals little more than a starvation diet, he noted, and it dramatically inhibits tumors. In one experiment, 26 of 50 well-fed mice developed mammary tumors after two years, compared with zero of 50 that were allowed only enough food to keep them going. Tannenbaum’s semi-starved animals not only lived longer but were more active, he reported, and had fewer “pathologic changes in the heart, kidneys, liver, and other organs.”
Most researchers paid scant attention to McCay’s and Tannenbaum’s results until the early 1990s, when the underlying genes were found. That’s when longevity research took off. The effect of calorie restriction on health and longevity has been shown to hold true not just for rodents but also for yeast, protozoa, fruit flies, worms, spiders, and maybe monkeys. The intervention prevents heart disease, cancer, diabetes, kidney disease, cataracts, Parkinson’s, and Alzheimer’s. It improves cholesterol profiles, lowers blood pressure, and prevents the deterioration of the immune system that naturally accompanies aging.
Calorie restriction may also preserve intellectual function, or at least what passes for intellectual function in laboratory rodents. The maximum life span of a normally fed lab mouse is a little more than three years. Semi-starved lab mice will not only live about 25 percent longer but will run a maze at three years with the facility of a well-fed mouse of six months.
Researchers cannot tell whether calorie restriction extends human life, because our species tends to live too long to make this kind of experimentation possible. But they are trying to see if it improves at least the biomarkers of health status—blood pressure, cholesterol profiles, and the like. Preliminary reports indicate that a reduced diet does produce such improvements, at least over the short term of the studies. But it is hardly a viable strategy for improving public health for an obvious reason: Precious few of us have the willpower—or desire, for that matter—to voluntarily subject ourselves to this kind of lifelong regimen. And clinicians working with anorexics have reported that after a decade or two, those with partial or subthreshold forms of the disorder—who maintain a diet some have compared to calorie restriction—show a failure to thrive, with damage to hearts, lungs and other organs.